PROJECT SUMMARY/ABSTRACT ? CANCER BIOLOGY PROGRAM The Cancer Biology (CB) Program, led by Chernoff and Testa is comprised of 19 Primary Members and 11 Collaborating Members. Program funding is $4.2M (project direct costs) annually, including $3.5M in peer- reviewed funding of which $1.9M is from the NCI. CB members have been highly productive and interactive during the past funding cycle, generating 534 publications, with 26% representing intra-programmatic and 33% representing inter-programmatic collaborations. The primary mission of the Cancer Biology (CB) Program is to determine how a normal cell becomes transformed and develops into a cancer. The Program now includes a range of studies that use cell-based and animal models, as well as patient-derived materials, to analyze and exploit altered signal transduction pathways in cancer cells, to explore interactions between tumor cells and their microenvironment, and to identify therapeutically useful properties of normal and transformed stem cells. These changes in scientific scope have been accompanied both by expansion in membership and inter- and intra-programmatic collaborations. The scientific platform of the CB Program is built on three pillars: altered cancer cell signaling, cancer stem cell biology, and the contributions of the stroma to cancer, with an overarching interest in how abnormalities in these domains promote the initiation and maintenance of cell transformation, invasion, and metastasis. The CB Program occupies a vital niche at Fox Chase Cancer Center (FCCC), allied to, but distinct from, the Molecular Therapeutics (MT) Program, and represents the core of molecular oncology research at this Institution. In addition, as the major home for signal transduction research at FCCC, the investigators in the CB Program are heavily involved in translational efforts to find useful new drug targets that regulate key neoplastic signaling pathways. Future plans center on strengthening, by means of strategic recruiting, the links between investigators studying aberrant signaling pathways in cancer cells (including cancer stem cells), and in the surrounding stroma, with the ultimate goal of translating these insights, in coordination with the MT Program, into clinical practice. All these activities are enabled by and heavily reliant upon Shared Resources as indicated by program usage of all 12 CCSG-supported Shared Resources.